: The hypothesis is that bFGF- and VEGF-induced angiogenesis in the fetoplacenta is modulated in part via an increase in production of NO which in turn activates the MAPK signal pathway and increases bFGF and VEGF expression, which further stimulates fetal placental angiogenesis. Three Specific Aims will be addressed using the well-characterized OFPAE cell line. AIM 1: to determine if exogenous NO-stimulated cell proliferation and migration are mediated in part via activation of the MAPK signaling pathway by treating cells with the NO donors in the absence or presence of the specific MAPK kinase inhibitor using proliferation and migration assays, as well as Western analysis and kinase activity assays to detect activation of MAPK. AIM II: To determine if bFGF and VEGF increase NO production by OFPAE cells by measuring total NO (nitrite/nitrate) concentrations in the culture media using a NO analyzer; and if bFGF- and VEGF-stimulated cell proliferation and migration are mediated in part via activation of the NO/MAPK pathway by treating cells with bFGF and VEGF in the absence or presence of L-NMMA or PD98059/UO126, using proliferation and migration assays, Western analysis and kinase activity assays; and AIM III: To determine if exogenous NO or bFGF- and VEGF-increased NO upregulates bFGF and VEGF expression by treating cells with three NO donors, as well as with bFGF and VEGF in the absence or presence of L-NMMA using ELISA, Western analysis and RNAse protection assays.